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2.7 Å cryo-EM structure of ex vivo RML prion fibrils

Manka, Szymon W; Zhang, Wenjuan; Wenborn, Adam; Betts, Jemma; Joiner, Susan; Saibil, Helen R; Collinge, John; (2022) 2.7 Å cryo-EM structure of ex vivo RML prion fibrils. Nat Commun , 13 , Article 4004. 10.1038/s41467-022-30457-7. Green open access

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Abstract

Mammalian prions propagate as distinct strains and are composed of multichain assemblies of misfolded host-encoded prion protein (PrP). Here, we present a near-atomic resolution cryo-EM structure of PrP fibrils present in highly infectious prion rod preparations isolated from the brains of RML prion-infected mice. We found that prion rods comprise single-protofilament helical amyloid fibrils that coexist with twisted pairs of the same protofilaments. Each rung of the protofilament is formed by a single PrP monomer with the ordered core comprising PrP residues 94-225, which folds to create two asymmetric lobes with the N-linked glycans and the glycosylphosphatidylinositol anchor projecting from the C-terminal lobe. The overall architecture is comparable to that of recently reported PrP fibrils isolated from the brain of hamsters infected with the 263K prion strain. However, there are marked conformational variations that could result from differences in PrP sequence and/or represent distinguishing features of the distinct prion strains.

Type: Article
Title: 2.7 Å cryo-EM structure of ex vivo RML prion fibrils
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-022-30457-7
Publisher version: https://doi.org/10.1038/s41467-022-30457-7
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Amyloid, Animals, Brain, Cricetinae, Cryoelectron Microscopy, Mammals, Mice, Prion Proteins, Prions
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Institute of Prion Diseases > MRC Prion Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Institute of Prion Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10152413
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